There are many diseases of importance in animal husbandry which are caused by chronic infectious agents which go through more than one life cycle during the infection. Many of these diseases are of financial importance to the owner of the animals, as many such diseases can cause effects to the animals which may not be apparent until the animal is prepared for market. These infectious agents may be bacteria, viruses or protozoa, but all have in common the property of multiple life cycles during the infection of the animal.
Chronic infections are of most importance to animals which have a short time for growing out prior to market. For example, poultry are generally marketed within weeks after hatching and this short time period does not permit the animals sufficient time to recover from a chronic infection prior to market if not treated in time. One particular chronic infectious agent which is of importance to the management of poultry flocks is coccidiosis caused by a protozoa of the genus Eimeria. Coccidiosis is a very common disease of poultry and there are several species of Eimeria which are known to cause such disease. The symptoms and severity of the disease are dependent upon the species of Eimeria with which the bird is infected with E.tenella, E.acervulina and E.maxima being three of the most prevalent species. Presently, poultry flocks are protected against coccidiosis by either immunization or the use of anti-coccidial chemotherapeutic agents with the most commonly utilized method for controlling coccidial infections being the use of anti-coccidial agents.
Such anti-coccidial agents are commonly ionophores, a class of antibiotics of complex structure although other chemotherapeutic agents are also used. Many such ionophores exhibit anti-coccidial activity, although the relative degree of activity varies from one agent to another. The ionophores which are commonly utilized for commercial control of coccidiosis include monensin, narasin, lasalocid and salinomycin. If anti-coccidial agents such as ionophores are utilized for control of coccidiosis in animals, it is necessary that the agent be continuously administered to the animal typically by being mixed with the feed used for raising the animal. Another problem associated with the use of anti-coccidial therapeutic agents is the possibility of resistant strains of Eimeria developing as a result of exposure to the anti-coccidial agent. There have, in fact, been reports of such resistant strains developing in the field.
As noted above, another method of controlling chronic infections, especially within poultry, is the use of immunization. At the present time, poultry hatchlings, within the first few days of life, are immunized against various diseases and the type of vaccine used for each disease dictates its method of administration. Attenuated vaccines are usually administered in the hatchery by injection at the time of sorting of the hatchlings from the hatching incubator into holding or transporting trays. Live vaccines are more commonly administered once the hatchlings are established in their brooding trays in the form of aqueous suspensions either sprayed on feed, added to the drinking water or the use of gelled form of vaccines such as taught in my PCT Application WO 96/25951 published Aug. 29, 1996.
Coccidiosis vaccines are at present comprised of live virulent strains of coccidia in a suitable carrier for administration, the coccidia being capable of causing a mild form of the disease and selected to be very anticoccidial susceptible.
Immunization does have some drawbacks, in that there may be antigenic diversity amongst species of the infectious agent as well as amongst strains of a particular species of the infectious agent. Thus, depending upon the antigenic diversity displayed in a field strain of the organism, immunization may not be quite so effective against that particular strain. In addition, organisms may undergo antigenic mutation to the point where the immunological response induced as a result of the immunization will not have sufficient specificity against the antigens present on the field strain to protect the animal against infection by the field strain. Use of live vaccines also results in the induction of a mild disease state in the animal from which the animal would normally recover, however, in immunosuppressed or immunoincompetent animals the degree of the disease state induced by the immunization may become significant. In such circumstances the uniformity of the therapy is affected with resultant variation in weight gain and feed conversion of the animals.
There have been attempts to overcome the above difficulty by the use of a combination of immunization and chemotherapy. U.S. Pat. No. 4,935,007, issued Jun. 19, 1990 to Eli Lilly and Company describes a method for control of coccidiosis involving both immunization and ionophore chemotherapy. The method of this patent involves orally administering to the animal at a neonate stage sufficient coccidial organisms to generate an immunological response while maintaining the animal free of any chemotherapeutic anti-coccidial. After the sporozoites have penetrated the host cells, an anti-coccidially effective dose of an ionophore is administered substantially continuously throughout the life of the animal.
While the method as described in U.S. Pat. No. 4,935,007 attempts to overcome the difficulties of the two methods of controlling coccidiosis, there are drawbacks associated with that method. The ionophore is administered to the animals commencing within 24 hours of immunization and continued throughout the life of the animal. Thus, the use of the method of U.S. Pat. No. 4,935,007 does not result in any significant savings over the traditional use of a chemotherapeutic agent alone. In addition, the commencing of the use of the chemotherapeutic agent within 24 hours of the immunization may not permit the full immunological response to occur, particularly if there are antigens which may not be expressed until later stages of the life cycle.
There thus remains a need for an improved method of controlling chronic diseases caused by infectious agents which undergo multiple life cycles in animals, and in particular, a method of controlling coccidiosis in poultry.